Parasympathetic Nervous Activity Associated with Discoordination Between Physical Acceleration and Heart Rate Variability in Patients with Sleep Apnea.

Sleep apnea syndrome (SAS) often accompanies alterations in heart rate variability (HRV). The severity of SAS is sometimes evaluated using the oxygen desaturation index (ODI). We hypothesized that effects of the autonomic nervous system could be involved in the coordination between HRV and physical acceleration during free movement in patients with SAS. Among 33 women aged 60 years or older, 19 had a high ODI (>5). Their HRV and physical acceleration were simultaneously obtained every minute for 24 hours. The low frequency/high frequency (LF/HF) ratio and the high frequency in normalized units (HFnu) were used as HRV indices. Low levels of %Lag0, defined as the percentage of the lag = 0 min in 1 h, indicated coordination between physical acceleration and HRV. Nineteen participants were divided into group A (high %Lag0 before sleep [n = 9]) or group B (low %Lag0 [n = 10]). In group B participants with a high ODI and low %Lag0 in the hour after waking, HFnu was significantly increased compared to that in group A participants with high ODI and high %Lag0 in the hour after waking (p < 0.05). These results suggest that close associations between high ODI and discoordination between HRV and physical acceleration may be due to higher parasympathetic nervous system activity after waking.

Does degree of alteration in effort sense caused by eccentric exercise significantly affect initial exercise hyperpnea in humans?

Previous research has shown an exaggeration in exercise hyperpnea 2 days after eccentric exercise (ECC). Enhancement in central command has been suggested as one candidate to account for this effect given that ECC-induced neuromuscular dysfunction increases relative exercise intensity, thus resulting in reinforcement of effort sense. The purpose of this study was, therefore, to elucidate whether the degree of alteration in effort sense caused by ECC affects exercise hyperpnea. Ten subjects performed 20-s single-arm extension-flexion exercises with weight strapped to the wrist, and ventilatory response was measured before (Pre) and 2 days after ECC (D2). Relative exercise intensity at Pre was 5 % of maximal voluntary contraction (MVC) of Pre, whereas that at D2 was 9 % MVC of D2 because of decline in muscle strength. Ventilatory responses were significantly exaggerated at D2 with a significant increase in effort sense. Although effort sense was significantly reduced during exercise at D2 when wrist weight was subtracted to match relative exercise intensity at Pre (5 % MVC of D2), ventilatory responses were still significantly higher than those of Pre. After the disappearance of post-ECC muscle damage, subjects performed the same exercise with weight added (9 % MVC of Pre) so that effort was equalized to match that of D2; however, no significant increase in ventilatory response was detected. The fact that the extent of change in effort sense caused by ECC-induced neuromuscular dysfunction did not affect ventilatory response at the onset of exercise after ECC may suggest that the exaggeration of ventilatory response after ECC is caused by mechanisms other than alteration of the central command.

Airborne transmission from a neonate with Netherton syndrome during an outbreak of MRSA.

We encountered a 4 month outbreak of methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection that was difficult to control despite implementation of standard prevention methods. A neonate with Netherton syndrome had accelerated scaling of the skin and continued positive results for MRSA from clinical samples. The results of air sampling suggested the possibility of airborne transmission. The MRSA outbreak stopped after the patient was transferred to an isolation room, suggesting that airborne MRSA can play a role in MRSA colonization. Isolation rooms should be considered in specific circumstances, as described in the present study.

Hyperferritinemia in neonatal and infantile human parechovirus-3 infection in comparison with other infectious diseases.

Human parechovirus-3 (HPeV-3) has been associated with severe clinical manifestations in neonates and infants in the form of sepsis or hemophagocytic lymphohistiocytosis (HLH)-like illness. To clarify the clinical features of HPeV-3 infection, we compared clinical signs and laboratory findings among enteroviruses (EVs), HPeV-3, and other infections. Participants were 26 febrile infants in whom EVs (n = 20) or HPeV-3 (n = 6) were isolated from throat swab or fecal specimens. Clinical and laboratory data were compared among EVs, HPeV-3, respiratory syncytial virus (RSV) infection (n = 15), and bacterial meningitis (n = 8) groups. Apnea was frequently seen in the HPeV-3 group although there were no significant differences in other clinical symptoms. Leukocyte count was significantly lower in the HPeV-3 group than in the EV and RSV group. Platelet count was significantly lower in the HPeV-3 group than in the RSV group. Serum ferritin levels in the HPeV-3 group (mean, 2437 ng/ml) and EV group (mean, 552 ng/ml) were significantly higher than in the RSV group (mean 237 ng/ml; P = 0.008 and P = 0.002, respectively). The frequency of patients with clearly high ferritin levels ≥1000 ng/ml was comparatively higher in the HPeV-3 group (4/6) than the EV group (3/20) (P = 0.03). In the HPeV-3 group, ferritin levels were high on Days 4-5. Elevated ferritin levels, decreased leukocyte and platelet counts could offer diagnostic clues to HPeV-3 infection in infant. These laboratory findings might be associated with aberrant immune response to HPeV-3, which could contribute to the development of sepsis or HLH-like illness in neonates.

Quantification of tumor vascularity with contrast-enhanced ultrasound for early response of transcatheter arterial chemoembolization for hepatocellular carcinoma: a report of three cases.

Many contrast-enhanced ultrasound (CE-US) studies have been conducted by qualitative analysis of blood flow, such as classification of enhancement pattern. We evaluated early response of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) by quantitative analysis of intratumoral vascularity with CE-US in three patients. Three patients (one man, two women) with HCCs were treated in July 2009. CE-US with perfluorocarbon microbubbles (Sonazoid) and CT were performed serially before and 5 days after TACE. Post-processing enhancement intensity on US was analyzed to determine mean transit time (s), time to peak (s), enhancement peak intensity (dB), and "A" (scaling factor) by ultrasound quantification software after the data were fitted to a gamma variate curve. Mean transit time was prolonged by TACE in all three patients. Mean transit time rates on CE-US were 64.3, 33.8, and 65.6%, respectively, whereas the avascular rates on CT were 59.07, 31.71, and 62.25%, respectively. Mean transit time rates on CE-US approximated avascular rates on CT. Mean transit time rate may quantitatively indicate the early response of HCC to TACE.

[Comprehensive geriatric assessment and cancer care-choice of treatment and in-home palliative care executed by using advance care planning].

Choice of treatment and in-home palliative care are important for the cancer care of the elderly. In recent years, comprehensive geriatric assessment (CGA), which has been developed as a multidimensional evaluation method for the elderly, has been attracting attention for cancer care as well. CGA can be a common language for the choice of treatment and in-home palliative care of elderly cancer patients. Also, advance care planning (ACP), is important as a process that supports decision making. In the future, better choices of treatment will become available, and in-home palliative care will be improved by carrying out cancer care using CGA, while continuously carrying out ACP as an organization, realizing a high quality of life (QOL) of the elderly.

[Role of home medical care support system in aged cancer patients' symptom relief and regional alliances].

The aim of this study was to evaluate the role of home medical care support system to relieve the symptom and regional alliances for elderly cancer patients. We investigated clinical parameters to study the features of this system. The home medical care support system is designed for patients who are B75-year-old with decrease in activities of daily living and severe dementia. The support system plays a significant role in patients with impaired oral ingestion, dyspnea, delirium, and a poor general status.

A conventional LC-MS method developed for the determination of plasma raltegravir concentrations.

Raltegravir belongs to a new class of antiretrovirals acting for a human immunodeficiency virus (HIV)-1 integrase inhibition. Clinical trials of this drug have demonstrated potent antiviral activity in both therapy naïve and experienced patients. Thus, raltegravir has become an important component of combination treatment regimens used to treat patients with multidrug-resistant HIV-1. The quantification of raltegravir in human plasma is important to support clinical studies and determine pharmacokinetic parameters of raltegravir in HIV-1 infected patients. Recently, the LC-MS/MS superfine system was developed to determine plasma concentration of raltegravir; however, the system needs to be delicately set and the equipment is very expensive. Therefore, we developed a conventional LC-MS method to overcome these difficulties. Subsequently the method was validated by estimating the precision and accuracy for inter- and intraday analysis in the concentration range of 0.010-7.680 microg/ml. The calibration curve was linear in this range. Average accuracy ranged from 97.2 to 103.4%. Relative standard deviations of both inter- and intraday assays were less than 10.4%. Recovery of raltegravir was more than 80.6%. This novel LC-MS method is accurate and precise enough to determine raltegravir levels in human plasma samples.

The validation of plasma darunavir concentrations determined by the HPLC method for protease inhibitors.

Darunavir (DRV) is a new protease inhibitor used to treat human immunodeficiency virus (HIV) type-1. The aim of this study was to validate the determination of plasma DRV concentrations using the HPLC method, a simple procedure for simultaneous determination of seven HIV protease inhibitors and efavirenz. The calibration curve was linear (range of 0.13 to 10.36 microg/ml). The average accuracy ranged from 100.7 to 105.6%. Both the interday and intraday coefficients of variation were less than 6.7%, which was similar to or much lower than previously reported values by the LC/MS/MS method. It is concluded that HPLC can be used to determine plasma DRV concentrations and routinely in the clinical setting; thus, this HPLC method enables further study of DRV pharmacokinetics in conventional hospital laboratories.

Determination of plasma tenofovir concentrations using a conventional LC-MS method.

The quantification of tenofovir, a nucleoside reverse transcriptase inhibitor prescribed once daily, in human plasma is important due to a recent increase in its use. HPLC, however, can not easily detect and quantify tenofovir because of interfering peaks. Therefore, we developed a rapid and conventional LC-MS method, validated by estimating the precision and accuracy for inter- and intraday analysis in the concentration range of 0.019-1.567 microg/ml. The calibration curve was linear in the described concentration range. Average accuracy ranged from 95.9 to 100.7%. Relative standard deviations of both inter- and intraday assays were less than 11.6%. Recovery of tenofovir was more than 80.2%. This novel method provides a conventional, accurate and precise way to determine tenofovir in human plasma samples.

No observable correlation between central nervous system side effects and EFV plasma concentrations in Japanese HIV type 1-infected patients treated with EFV containing HAART.

The present study assessed the relationship between central nervous system (CNS) side effects and plasma concentrations of efavirenz (EFV) in Japanese HIV-1-infected patients. Subjects consisted of 69 HIV-1-infected patients (57 therapy-naive and 12 therapy-experienced patients) being treated using EFV in combination with other antiretroviral agents at the outpatient HIV clinic. Successful virological treatment was achieved in 61 patients. Eight patients discontinued EFV containing therapy because CNS symptoms did not resolve (four patients), EFV-specific mutations were detected (two patients), or skin rash was observed (two patients). Mean EFV plasma concentration for 61 effectively treated patients, measured at 15 h postdosing, was 2.42 microg/ml (range: 0.78-6.82 microg/ml). This EFV concentration range contributed to suppressed viral load in these Japanese patients. Adverse CNS effects were observed in 19 patients soon after therapy onset. These effects disappeared within 1 month except for four patients who suffered severe CNS side effects. Mean EFV plasma concentrations were not significantly different between subjects with (2.45 +/- 1.08 microg/ml) and without (2.42 +/- 1.40 microg/ml) CNS side effects. We concluded no correlation existed between the plasma EFV concentration and the emergence of CNS side effects in Japanese HIV-1-infected patients. Further investigations, enforced with the drug concentration measurement at earlier time points and more appropriate assessment of CNS symptoms, are required.

Beneficial effect of GB virus C co-infection in Human Immunodeficiency Virus type 1-infected individuals.

Several reports have documented a better prognosis for HIV-1-infected patients co-infected with GBV-C, while other reports have contradicted such findings with the result that this issue remains controversial. We attempted to clarify the complicated status of the effect of GBV-C co-infection on HIV-1-infected patients. GBV-C RNA was detected in 37 samples in 182 HIV-1-infected patients (20.3%) using RT/nested PCR. Of these, 3 were determined to be GBV-C genotype 1, 12 were genotype 2, and the remaining 22 were genotype 3. The GBV-C viral load quantified by real-time PCR ranged from 7.8x10(3) to 3.3x10(6) copies/ml. Weakly negative correlation was observed between GBV-C viral load and HIV-1 viral load in 19 HAART-naïve patients, indicating that a higher GBV-C viral load is associated with a greater suppression of HIV-1 replication. A previously published in vitro study suggested that GBV-C infection would induce up-regulation of RANTES, leading to suppression of HIV-1 replication. However, in our present study, the blood RANTES level was significantly lower in the GBV-C co-infected group than in the uninfected group (190-9,959 vs. 264-31,038 pg/ml, P=0.004). Our results suggested that a suppression of HIV-1 replication by GBV-C co-infection is not mediated by up-regulated RANTES, and thus call for another as yet unknown factor.

Conventional HPLC method used for simultaneous determination of the seven HIV protease inhibitors and nonnucleoside reverse transcription inhibitor efavirenz in human plasma.

We developed a simple HPLC method for the simultaneous quantitative determination of seven HIV protease inhibitors: amprenavir (APV), atazanavir (ATV), indinavir (IDV), lopinavir (LPV), nelfinavir (NFV), ritonavir (RTV), saquinavir (SQV), and a nonnucleoside reverse transcription inhibitor, efavirenz (EFV). This method involves a rapid liquid-liquid drug extraction from plasma, the use of an isocratic elution on a reversed-phase C18 column, and an ultraviolet detection at a single wavelength (205 nm). The mobile phase consisted of 39% 50 mM phosphate buffer (pH 5.9), 22% methanol and 39% acetonitrile. Forty-eight samples could be measured in one day since the runtime of one sample is 30 min. The assay has been validated over a concentration range of 0.05 to 12.20 microg/ml for APV, 0.09 to 12.05 microg/ml for ATV, 0.05 to 12.01 microg/ml for IDV, 0.12 to 12.36 microg/ml for LPV, 0.18 to 12.20 microg/ml for NFV, 0.12 to 12.33 microg/ml for RTV, 0.12 to 12.06 microg/ml for SQV, and 0.05 to 12.17 microg/ml for EFV. Calibration curves were linear in the described concentration ranges. The average accuracy ranged from 97.2 to 106.8%. Both the interday and intraday coefficients of variation for all drugs tested were less than 8.5%. This method provides a simple, accurate, and precise method for the therapeutic drug monitoring of the seven protease inhibitors and EFV in clinical routine use.